# US 8,771,733 B2 · Pharmaceutical composition containing an anti-nucleating agent > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,771,733 B2 - Document ID: US8771733B2 - Status: Granted - Kind: B2 - Application number: 11/792,190 - Filed: 2005-12-02 - Published: 2008-05-22 - Granted: 2014-07-08 - Earliest claimed: 2004-12-03 - Assignees: Merck Sharp & Dohme Corp. - Applicants: Maria T. Cruanes; Wei Xu; Laura M. Artino; Honggang Zhu - Inventors: Maria T. Cruanes; Wei Xu; Laura M. Artino; Honggang Zhu - Web page: https://patentgrep.com/patent/US8771733B2 ## CPC - A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine - A61K 9/2009: {Inorganic compounds} - A61K 9/2013: {Organic compounds, e.g. phospholipids, fats} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61P 31/18: for HIV - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Pharmaceutical compositions suitable for oral administration in solid dosage forms are described. The compositions comprise an effective amount of a drug compound in the form of a salt, wherein the drug salt is characterized by conversion to a less soluble form of the drug compound under certain pH conditions, and an anti-nucleating agent. ## Claims ### Claim 1 A pharmaceutical composition for oral administration as a solid dose, which comprises: (a) from 2 to 15 wt. % of an anti-nucleating agent which comprises a hydroxyalkylcellulose, and (b) from 5 to 75 wt. % of a potassium salt of Compound A, wherein Compound A is: ### Claim 2 (depends on 1) The pharmaceutical composition according to claim 1, wherein the potassium salt of Compound A is Form 1 potassium salt of Compound A. ### Claim 3 (depends on 1) The pharmaceutical composition according to claim 1, wherein the anti-nucleating agent comprises hydroxypropylmethylcellulose. ### Claim 4 (depends on 1) The pharmaceutical composition according to claim 1, which further comprises a first diluent, a second diluent, a disintegrant, and a lubricant. ### Claim 5 (depends on 4) The pharmaceutical composition according to claim 4, wherein: the anti-nucleating agent is hydroxypropylmethylcellulose; the first diluent is microcrystalline cellulose; the second diluent is lactose or dibasic calcium phosphate; the disintegrant is croscarmellose sodium; and the lubricant is magnesium stearate. ### Claim 6 (depends on 5) The pharmaceutical composition according to claim 5, wherein: the microcrystalline cellulose is employed in an amount of from 10 to 85 wt. %; the lactose or dibasic calcium phosphate is employed in an amount of from 10 to 85 wt. %; the croscarmellose sodium is employed in an amount of from 1 to 10 wt. %; and the magnesium stearate is employed in an amount of from 0.5 to 10 wt. %. ### Claim 7 (depends on 6) The pharmaceutical composition according to claim 6, wherein the potassium salt of Compound A is Form 1 potassium salt of Compound A. ### Claim 8 (depends on 6) The pharmaceutical composition according to claim 6, wherein the composition is encapsulated or compressed into a tablet. ### Claim 9 (depends on 8) The pharmaceutical composition according to claim 8, wherein the potassium salt of Compound A is employed in an amount of from 5 mg to 900 mg. ### Claim 10 (depends on 4) A process for preparing a compressed tablet having a pharmaceutical composition according to claim 4, wherein the method comprises: (A) blending a mixture of the Compound A potassium salt, the anti-nucleating agent, none or all or a first portion of the first diluent, the second diluent, the disintegrant, and a first portion of the lubricant; (B) either (i) compressing the blended mixture to form one or more slugs or (ii) rolling the blended mixture to form a compact, and then sizing the resulting one or more slugs or the resulting compact to form granules; (C) blending the granules with all or none or the remaining portion of the first diluent and the remaining portion of the lubricant; and (D) compressing the lubricated granules of Step C to obtain the tablet. ### Claim 11 (depends on 10) The process according to claim 10, wherein: the anti-nucleating agent is hydroxypropylmethylcellulose; the first diluent is microcrystalline cellulose; the second diluent is lactose or dibasic calcium phosphate; the disintegrant is croscarmellose sodium; and the lubricant is magnesium stearate. ### Claim 12 (depends on 11) The process according to claim 11, wherein: the microcrystalline cellulose is employed in an amount of from 10 to 85 wt. %; the lactose or dibasic calcium phosphate is employed in an amount of from 10 to 85 wt. %; the croscarmellose sodium is employed in an amount of from 1 to 10 wt. %; and the magnesium stearate is employed in an amount of from 0.5 to 10 wt. %. ### Claim 13 (depends on 4) A process for preparing a compressed tablet having a pharmaceutical composition according to claim 4, wherein the method comprises: (A) wet granulating a mixture of Compound A potassium salt, the anti-nucleating agent, the first diluent, the second diluent, and the disintegrant, and then optionally milling the wet granulated mixture; (B) drying the wet granulated mixture of Step A; (C) milling the dried mixture of Step B; (D) lubricating the milled mixture of Step C with the lubricant; and (E) compressing the lubricated mixture of Step D into a tablet. ### Claim 14 (depends on 1) A method for improving the pharmacokinetics of a compound of Formula I as recited in claim 1 orally administered in the form of a base salt, wherein the method comprises administering the compound base salt as a component in a solid-dosage pharmaceutical composition that includes an anti-nucleating agent. ### Claim 15 (depends on 1) A method for the treatment of HIV infection in a subject in need thereof which comprises administering to the subject the pharmaceutical composition according to claim 1. ### Claim 16 (depends on 6) The pharmaceutical composition according to claim 6, wherein: the potassium salt of Compound A is employed in an amount of from 5 to 60 wt. %; the microcrystalline cellulose is employed in an amount of from 15 to 75 wt. %; the lactose or dibasic calcium phosphate is employed in an amount of from 10 to 50 wt. %; the croscarmellose sodium is employed in an amount of from 1 to 5 wt. %; and the magnesium stearate is employed in an amount of from 0.5 to 3 wt. %. ### Claim 17 (depends on 16) The pharmaceutical composition according to claim 16, wherein the composition is encapsulated or compressed into a tablet. ### Claim 18 (depends on 16) The pharmaceutical composition according to claim 16, wherein the potassium salt of Compound A is Form 1 potassium salt of Compound A. ### Claim 19 (depends on 18) The pharmaceutical composition according to claim 18, wherein the composition is encapsulated or compressed into a tablet. ### Claim 20 (depends on 3) The pharmaceutical composition according to claim 3, wherein the potassium salt of Compound A is employed in an amount of 50 wt. % and the hydroxyproylmethylcellulose is employed in an amount in a range of from 2 wt. % to 15 wt. %. ### Claim 21 (depends on 20) The pharmaceutical composition according to claim 20, wherein the hydroxyproylmethylcellulose is employed in an amount of 5 wt. %. ### Claim 22 (depends on 3) The pharmaceutical composition according to claim 3, wherein the hydroxyproylmethylcellulose is a low-viscosity hydroxypropylmethylcellulose. ### Claim 23 (depends on 22) The pharmaceutical composition according to claim 22, wherein the potassium salt of Compound A is employed in an amount of 50 wt. % and the low-viscosity hydroxyproylmethylcellulose is employed in an amount in a range of from 2 wt. % to 15 wt. %. ### Claim 24 (depends on 23) The pharmaceutical composition according to claim 23, wherein the low-viscosity hydroxyproylmethylcellulose is employed in an amount of 5 wt. %. ### Claim 25 (depends on 1) The pharmaceutical composition according to claim 1, wherein the potassium salt of Compound A exhibits improved pharmacokinetic properties when administered as a component of this composition.